A phase 2 trial of fludarabine and mitoxantrone chemotherapy followed by yttrium-90 ibritumomab tiuxetan for patients with previously untreated, indolent, nonfollicular, non-Hodgkin lymphoma

Cancer. 2008 Feb 15;112(4):856-62. doi: 10.1002/cncr.23236.

Abstract

Background: A prospective, single-arm, open-label, nonrandomized Phase 2 study of combined fludarabine and mitoxantrone (FM) plus radioimmunotherapy was conducted to evaluate efficacy and safety in patients with untreated, indolent, nonfollicular non-Hodgkin lymphoma (NHL).

Methods: Between February 2005 and June 2006, at their institute, the authors treated 26 eligible patients with previously untreated, indolent, nonfollicular NHL (10 marginal zone lymphomas, 8 lymphoplasmacytic lymphomas, and 8 small lymphocytic lymphomas) using a novel regimen that consisted of 6 cycles of FM chemotherapy followed 6 to 10 weeks later by yttrium-90 (90Y) ibritumomab tiuxetan.

Results: After FM chemotherapy, the overall response rate was 80.5% and included a 50% complete remission (CR) rate (13 patients) and a 30.5% partial remission (PR) rate (8 patients). Of the 20 patients (13 with CR and 7 with PR) who were evaluable (at least a PR with normal platelet counts and bone marrow infiltration <25%) for subsequent 90Y ibritumomab tiuxetan, 100% obtained a CR at the end of the entire treatment regimen. At a median follow-up of 20 months, the estimated 3-year progression-free survival rate was 89.5%, and the estimated 3-year overall survival rate was 100%. The 90Y ibritumomab tiuxetan toxicity included grade >or=3 hematologic toxicity in 16 of 20 patients; the most common grade >or=3 toxicities were neutropenia (11 patients) and thrombocytopenia (16 patients) (adverse events were graded according to the World Health Organization criteria for toxicity). Transfusions of erythrocytes and/or platelets were given to 5 patients.

Conclusions: The current study established the feasibility, tolerability, and efficacy of the FM plus 90Y ibritumomab tiuxetan regimen for the treatment of patients with untreated, indolent, nonfollicular NHL.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Neutropenia / chemically induced
  • Radioimmunotherapy / adverse effects
  • Radioimmunotherapy / methods*
  • Survival Analysis
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Yttrium Radioisotopes / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Yttrium Radioisotopes
  • ibritumomab tiuxetan
  • Mitoxantrone
  • Vidarabine
  • fludarabine